There is considerable interest in FDA regulatory reform here in the U.S. for stem cell therapies. The goal is to get new treatments to patients faster, but is there a way to do that without sacrificing proven safety and efficacy?

You need convincing data on both safety and efficacy or speed becomes dangerous.

A group called the Bipartisan Policy Center (BPC) recently issued a report related to these central questions of American regulation of new stem cell products. You can see a screenshot from the cover of the report above. The report argues for a new paradigm of FDA regulation of stem cells with reduced regulatory steps.

While I support the notion that there need to be reforms at the FDA related to regulation of stem cell-based therapies, looking at it scientifically based on the current state of stem cells in the US, the potential cons of what the BPC report recommends outweigh the possible pros.

Pursuing the BPC plan at this time would be a high-risk experiment that could yield benefits and harms or most likely some complicated combination of both, but again I believe the risks are considerable making the report imprudent overall. Others, including some stem cell colleagues feel otherwise so I think a lively debate could prove to be healthy on this topic.

Below I outline the potential pros and cons as I see them.

Possible Pros. The report does a good job of highlighting the potential positives that could come from the proposed regulatory reforms:

Speeding therapy to patients. The most prominent possible upside would be speed in the form of getting new stem cell therapies into patients more quickly.

Helping American competitiveness. A second positive, depending on one’s perspective, would be possibly increasing American competitiveness in the global stem cell arena.

Generating money. Finally, because the plan specifically allows companies and non-profits to charge for experimental stem cell therapies, those entities doing the research could benefit from that income and in theory that could support furthering of the research.

Possible Cons. Perhaps because the report is intended to convince readers of its thesis that we need regulatory reforms that accelerate getting stem cell therapies into patients, it doesn’t discuss risks or potential cons to the recommendations. However, as a scientist I find it disappointing that the report ignores potential risks to its recommendations.

In science, especially clinically-related science, we cannot afford to ignore risks. For this reason, the report reads as being somewhat more political than scientific, perhaps not an entire surprise given that two former politicians led the way on it.

The significant cons to the recommendations if implemented include the following:

Risk of medical harm. When the BPC Plan on Stem Cells characterizes stem cells as different than drugs, it goes against decades of science. Biological drug products released onto the for-profit market without full vetting will pose some risks of increased medical harm to consumers. For instance, dropping the requirement for Phase III trials as they recommend in some cases would be risky. Ignoring that increased risk seems unwise as it needs to be part of the equation and discussion in risk-benefit analysis for any new regulatory paradigm.

Charging research subjects. There is a tradition in biomedical science of not charging patients for receiving experimental treatments. In fact, more often patients are paid to be subjects. I believe that taking patients’ money to allow them access to an unproven, experimental treatment is unethical. Unfortunately, some are already doing this in the U.S., but the BPC report if implemented would make that practice far more common. I understand that the translational stem cell field could benefit from generate some funds in support of clinical studies, but this shouldn’t come from patients.

Unintentionally helping predatory clinics. The BPC recommendations, while still requiring some approvals such as an IND, are significantly weaker than the current regulatory framework. From what I’ve heard from the for-profit clinic folks, they see this report, even if it isn’t implemented and even though it still requires an IND, as a victory. Why? Because they believe that the report represents a shift in their direction ideologically. They see it as somewhat of a capitulation by the academic and biotech sectors toward the notion that the FDA is wrong on stem cells. This is very worrisome. The report even uses some of the memes of the stem cell clinics and their proponents such as arguing, as mentioned earlier, that stem cells are not drugs and that patients have a right to get transplants of their own cells even if those cells have been turned into a product.

Encouraging global deregulation. This plan could also be taken as a template in many other countries around the world for their own regulatory changes toward weaker oversight, which could amplify risk to thousands more patients globally.

Fostering a sense of potentially unhealthy, international competition. I’m an American and we have a great country here, but I have reservations about framing stem cell regulatory debates in a nationalistic or political kind of way that could lead to harmful competition. Again to me the BPC report comes off as too political and not scientific enough, and that is especially true when it discusses national priorities. There is a palpable sense in the report that those who wrote it are worried about the US falling behind Japan on stem cells.

Overall, I recommend that the FDA not adopt the BPC recommendations because that would be just too risky and raises serious bioethical concerns. We need a different plan that more cautiously approaches regulatory changes and openly acknowledges that there would be risks.

One such plan I could potentially support would be focused squarely on a relatively simpler path to FDA triggering of Fast Track, Accelerated or Priority Review or Breakthrough Therapy Designation for stem cells.

23 Comments

Paul, my only comment is that it is a pity you don’t put as much emphases on the possible pros as you have done on the significant cons. I think it shows who’s side you are on. Those of us wanting treatment and either can’t get it because of all the hype about it might not be safe which I believe is a breach of ones civil liberties or because the clinics all under the government/FDA thumb. I wish to have treatment for my heart and willing to pay for treatment that is currently being tested at the Texas Heart Hospital. Yes I could join the trial but why would I want to waste thousands of dollars to find I had a placebo. This procedure has been done before and the people who have received it have all had improvement. Any treatment that are in trials by respectable clinics or hospitals should allow people the opportunity to join the trials and receive the treatment so long as they are willing to have follow up check ups. This would not only offer the patients some hope of better health but also see how they match to any proper clinical trials. Surely that would be a significant pro!!!!!

@David,
I get your point on me highlighting the cons mostly, but I felt the creators of this report did a very thorough job highlighting the pros and frankly they entirely excluded any cons. They did a remarkable job on that. Also, I kind of assumed readers would also go and read the actual report too, which again paints an awfully rosy picture.

I don’t believe that most of the clinics care one bit about your or anyone else’s civil liberties.

They want your $$$ and that’s above all else.

If you’ve ever heard of a clinic doing this kind of stem cell treatment at cost (i.e. no profit, but just covering their expenses) let me know as that would be big news.

As for placebo, I get your point that you don’t want to get a placebo and I wouldn’t either in certain circumstances, but without those kinds of controls us scientists don’t really learn what the heck is the real deal for any given experimental treatment being tested.

And that brings up the other point that these stem cell drugs need to be pre-tested for safety and efficacy very carefully before they are unleashed on the market or a lot of people can (A) get hurt and (B) waste their hard earned money.

@paul. I generally agree with your point of view. However, there is one simple change that would make the overall recommendations more palatable, IMO. Just eliminate the one proposal that allows patients to pay for participating in clinical trials. That is the biggest problem here because that provision could provide the wrong motivations and I agree with you that patients should not pay for unproven treatments. Other than that there is a strong body of evidence that adult stem cells, especially autologous, are safe when administered properly. The regulations should be streamlined to recognize this simple reality. Japan has taken the lead here and the FDA or congress should do something too.

@WST,
The $ is indeed a big issue. If memory serves the report didn’t say something like, “these treatments should be covered by insurance” so in that context I think patients would be expected to pay to be a clinical trial participant themselves. Again, that’s already happening even at some universities apparently, but in my view it is wrong.
However, there are other issues too such as delaying the requirement for a BLA for 3 years. Many folks out there interested in developing stem cell therapies are good citizens, but many others and they could try to take advantage of this and other loopholes, weaker regs, etc.

@WST – “safe when administered properly” Yes, I see this in much of the literature, but I also see reports of severe adverse effects, and even immune responses to autologous cells. So when is safe, safe enough?

And what can the FDA recommend as “administered properly” in a guidance document, until there are clear data across i) different populations regarding ii) non-homologous use of iii) stem cell from different sources from iv) different isolation, expansion and storage procedures, and a bunch of other variables.

And are you proposing streamlining regulations after clinical proof of safety and efficacy or in the absence of such proofs?

@Jeff,
I share your concerns. I also feel like there are several key catch phrases in the BPC report that make big assumptions. Who decides what is “proper administration”? I also think the crafters of the report make broad conclusions based on limited data that adult stem cells are universally safe somehow.
Paul

@WST – actually, it was the recommendations on page 11 that provoked my concerns in the first place. From a scientific, clinical and practical point of view, the document presents a collection of presumptions and generalisms with no indication of how these recommendation are operatively defined.

One example: “1. Strengthening the rights of patients to be treated with their own cells or allogeneic cells that do not induce an adverse immune response…”

Do they mean that autologous cells never induce adverse immune responses? (that would simply be wrong). Or that patents should be allowed treatment once these cells have demonstrated sufficient safety data in appropriate and controlled clinical trials for the therapeutic regimen in question? (which is an FDA standard)?

Many such presumptive statements are made and I think it’s because the authors are less concerned with (or don’t have the scientific background to assess) how therapeutic parameters such as, “…do not induce adverse immune response” are actually defined.

I also believe that there must be new regulations made for the testing and approval of regenerative medicines, But this document uses too many “presumptive” adjectives and advances the discussion very little.

@Paul – yes they do, and looking deeper the authors seem well aware of the “woolliness” they create. Take the line, “…at least preliminary rigorously obtained and well-documented clinical evidence of efficacy.”

What is that? A sentence that sounds like the one we need – peer-reviewed data from controlled clinical trials demonstrating relevant and significant efficacy over the standard-of-care. But the first statement could easily be claimed for a few patients amongst many that self-report an amazing recovery and is published in any journal. Clinical efficacy doesn’t even need to be an approved clinical trial.

“I don’t agree that: “When the BPC Plan on Stem Cells characterizes stem cells as different than drugs, it goes against decades of science.””

Autologous bone marrow derived stem cells have never been considered a drug -as long as they are not expanded. Should there be a distinction between BM derived cells and SVF? I don’t think so because neither are drugs. But I still believe that patients should be protected to some extent because when they visit a stem cell clinic, they have no way of knowing whether the method used to extract the SVF yields a viable, pure and adequate cell count. Not to mention whether there is enough evidence to prove it works for the indication being treated. That’s why I don’t believe that doc should be collecting fees.

@WST
I don’t see that a cell becomes a drug when it is expanded. It’s still a cell. For now the FDA hasn’t moved in on autologous marrow derived MSC without expansion — but I bet they will whenever they have another capricious urge…

Should there be a distinction between BM derived cells and SVF? Of course, they’re different types of cell. And there should be distinctions in view of the various ways in which a particular type of cell is used. Different tools for different jobs, not one FDA hammer for them all!

As for protecting the patients, hear hear. But FDA prohibition is not protection.*** The medical community should be working hard to make sure that they do a good job for their patients. (I can see that some of them are…)

*** Let me give you a very specific example of why FDA prohibition is not protection. Take the instance of a traumatic joint injury, to the meniscus or ACL, for example. The standard option was to send the patient off for surgery. Regardless of whether the medical system was private or state controlled, such things are accepted practice and done willy-nilly. Way back in 1948 a guy called Fairbank published a paper in The Journal of Bone and Joint Surgery. Now, anyone who reads that paper would have very serious doubts about the surgical option. I sure as hell wish I had found that paper before a surgeon messed me up back in 1972! Of course, the inconvenient truth was swept under the rug. You can understand why it would be swept under the rug. (Doctors want to do something, what else?)

Fast forward to today. There are options. My reading of the literature is that BM-derived MSC are probably the best option (culture expanded, better, probably). There are some fairly large studies published regarding safety (for particular methods of orthopaedic application). There is a smattering of evidence for good outcomes. OK, not enough to impress Paul and the FDA, I guess, but it’s more than nothing… The good news is, having some sort of an option is finally encouraging people (including surgeons) to reassess what I would call long-standing, harmful, barbaric, surgical practice.

Now Paul takes a very particular view about “proving” a therapy is both safe and effective, according to the FDA way of doing things. I take a different view. From my point of view what matters most is that it is safer (and/or better) than the other options that people are being subject to.

You can save people harm by providing an alternative. Even a placebo can save someone from harm. (Actually, often a placebo saves people from harm!)

Conversely, prohibition can cause medical harm.

It is on this last point that my calculation substantially differs from Paul’s calculation… and from FDA orthodoxy.

The biggest problem with the FDA is that they will lose their jobs if too many people get sick and die from experimental treatments of newly approved drugs, yet won’t get fired for delaying treatments that would have saved people if delivered sooner.

Gene therapy could create a healthier world. But which country will tap its potential first?
Since 1989, labs around the world have initiated more than 2,200 clinical trials testing gene therapies, but only a few studies have resulted in government-approved applications. The United States has led the way in this research to treat or prevent disease, but Washington has authorized not one therapy for commercial development.
Who’s Treating What? http://foreignpolicy.com/2016/03/17/decoder-gene-therapy-breakthrough/?

@Brian, @Paul – “When the BPC Plan on Stem Cells characterizes stem cells as different than drugs, it goes against decades of science.”””

Actually this was Paul’s statement and I meant to respond to him that autologous MB stem cells have never been considered a drug. I agree with you Brian that many orthopedic surgeries are not supported by science. One example is meniscus surgery. This large study http://www.ncbi.nlm.nih.gov/pubmed/24369076 proved it was ineffective and, IMHO, probably a bad idea for longer term knee health. However, that doesn’t justify allowing unproven stem cell therapies to be used upon the gullible public.

My best advice is to do a hell of a lot of due diligence before you do any medical procedure or take any drug and be careful of your sources.

@WST — Totally agree that due diligence is very important. I go further. I think that patients have a responsibility to become educated about any disease that they suffer from and that doctors have a responsibility to assist in that processes in whatever way they can. (I think that things are moving, slowly, in the correct direction… so I preach to the choir.)

“Moreover, when you take out patient funding, it removes my concern that patients, many of whom are technically unable make highly informed decisions given all the variables, can be taken advantage of out of desperation.”

We are more informed about our own disease and adult stem cell treatment that we’ve received, than many of our doctors! I’ve had some great conversation with my primary care doc, OBGYN etc… who admit they really don’t know much about adult stem cell treatments. We are in touch with thousands of patients who receive therapy! We talk to our stem cell doctors regularly! Patients have shared years of research with each other. Why don’t you actually talk to some patients to get the facts correct before you generalize that MANY patients are unable to make highly informed decisions about their health! A paternalistic attitude is something we’ve dealt with for a long time. Here’s an article we recently wrote about the patient plight.

We agree with @zchick1836 (who is Dr. Jennifer Ziegler) she showed us how stem cells achieving fantastic healing in multiple sclerosis relapsing remitting disease on her website http://www.patientsforstemcells.org. We read all of pages and are now understanding how stem cells are working to cure our illnesses and are known well to be safe.

We also have thanks for Dr. Ziegler for recommendation of stem cell clinic in Mexico for therapy of multiple sclerosis relapsing remitting. My mother now receive stem cell therapy with treatment of autologous adipose-derived mesenchymal stem cells. Doctors at clinic saying we will have results in few months.

Excellent news @Hassan I was happy to share information with you on the reputable stem cell clinics patients are seeing results from with MS. I’m also glad to know your family made a decision on where to go. I suspect a language barrier might be involved, as I am a stem cell patient myself, and not a doctor. It took me a long time to figure out who all the interested parties were after I got stem cell treatment for MS, and I wasn’t dealing with a language barrier! Good wishes to your mom for quality of life improvements.

“”Moreover, when you take out patient funding, it removes my concern that patients, many of whom are technically unable make highly informed decisions given all the variables, can be taken advantage of out of desperation.””

I am not sure what social level you belong to or what Stonehenge men applauded your low intellect as brilliance personified….your statements are rank below-stupid and insulting to patients and families who often make many months, if not years, of elaborate efforts to talk to doctors, other patients, consult literature and strive to verify online information before they make an informed decision to step into a private stem cell clinic, often times after exhausting all options. You have the nerve to insult all these folks, even as they go through failure after failure of FDA-approved “safe & effective” drugs AKA poisons. Or would you rather think it is perfectly justified if FDA-approved clinical trials inject 5 billion stem cells into children brains or push through snake oil charlatan treatments as evident in the Autism trial. Is that “informed content” for your academic types?